Cancer is the second leading cause of death among veterans, and the Veterans Health Administration estimates that there exist >170,000 cancer patients within in the VA system. Moreover, approximately 50,000 new cases of cancer are diagnosed each year. With the aging of the veteran population, this number is expected to increase causing a concomitant encumbering of healthcare resources. Lung cancer, which is the leading cause of death in both men and women in industrialized countries (an estimated 28% of all cancer deaths in the USA), is also the leading cause of cancer death in the veteran population. Indeed, many veterans continue to acquire tobacco addiction during their military service even though tobacco abuse is currently discouraged by the military. Hence, there exists a very large percentage of high-risk current and former smokers cared for in the VA health care system that would benefit from advances in therapeutic molecular targeting in the treatment of lung cancer. Also, lung cancer is also linked to the well-established lung carcinogens, Agent Orange, Asbestos, and Ionizing Radiation, which exposure to these agents are often are service-connected disorders. To address this issue, the research of the Chalfant Laboratory focuses on non-small cell lung cancer (NSCLC), which represents the majority of lung cancers, carries a poor prognosis with a median survival of less than 12 months, and has a cumulative five-year survival rate of approximately 15%. The research of the Chalfant Laboratory is tailored to identify new cellular targets for the development of new treatments for this deadly disease, which are thus, directly relevant to the patient care mission of the Department of Veterans Affairs. Indeed, biomedical research investigating new strategies for the development of lung cancer therapeutics has tremendous potential benefit to veterans, many of whom no longer smoke, yet remain at high risk for NSCLC. The Chalfant Laboratory focuses on two major, but diverse areas of basic science in regard to Cell Biology, Microbiology, and Molecular Biology. Specifically, the Chalfant Laboratory studies mechanisms of cell signaling associated with both bioactive lipids and RNA splicing with a focus on both basic science mechanisms as well as in many cases clinical translation. In regard to RNA splicing research, the Chalfant Laboratory has identified key RNA splicing events and signaling mechanisms mediating the tumor maintenance of NSCLC cells. The applicant is further merging these finding with novel lipid signaling events linked to cell survival. The applicant, Dr. Chalfant, has been very productive with >100 peer-reviewed publications, and he has been a distinguished member of the VA system for 17 years. His research work is supported by several NIH/VA funded projects and currently, he has one VA Merit Review award and three NIH funded projects (2-R01 and 1- U01). He has trained more than 40 trainees at very levels with a number of them currently faculty members at various institutions with funded research programs. The applicant is an unselfish mentor of young investigators allowing them to act as co-corresponding authors on numerous publications for the betterment of their careers. The applicant continues to be a leader in his scientific field as shown by appointments to several Editorial Boards and National Committees, which include: the editorial boards of the Journal of Lipid Research. Molecular Cancer Research, and the Journal of Biological Chemistry, formal membership on the Cancer and Molecular Pathobiology Study Section of the National Institutes of Health, and formal membership on the Oncology A Study Section of the Veterans? Administration. These areas of research also led to the communication of the 2011 ASBMB Avanti Junior Investigator Award for Lipid Research to Dr. Chalfant. The applicant has also extensively collaborated with numerous investigators in funded program projects and scientific publications. In summary, the applicant?s scientific contributions are vitally important to the VA mission. He has made ground breaking discoveries in the field of NSCLC, RNA Splicing, Lipidomics, and Lipid Signaling and has also provided significant resources to the scientific community and the VA system.